Opinion

Scaled upshot: Meta-analysis unplugged

By RAJGOPAL NIDAMBOOR

You need not go too far to glean insights from paradoxical scientific studies.

To highlight a few examples: the famed oat bran, wheat grass, garlic, caffeine saga or the fascinating coconut story. It proves a point – that the promise of science as an arbiter of truth may not be all too sound.

The whole drama began in the early 1980s, when research teams, taking a 'cue' from past research and expanding on it, suggested that the water-soluble fibre in oat bran could lower cholesterol levels. Things reached the crescendo when Robert E Kowalski's book, 8-Week Cholesterol Cure, eulogised some of the 'wonderful' medicinal qualities of oat bran.

This bid fair to yet another scientific review of high-fibre diet studies, with oat bran and beans. Oat bran was bestowed with a 'merit' certificate by The Journal of the American Medical Association (JAMA) – this was a major scientific avowal, emerging as it did from a well-respected, peer-reviewed publication. It highlighted why oat bran was special – because it was extremely 'cost-effective' than any other treatment 'form' available for high cholesterol levels. The spin-off was imminent. Sales of oat bran reached astounding levels, so much so there was trouble keeping in step with its ever-increasing demand.

But the 'magic' oracle of the 'one-piece' oat bran orchestra slid and tumbled down the scientific alley, when a study, in the United Kingdom, demonstrated that refined wheat had just as much healing effects as oat bran on high cholesterol readings. Soon enough, conflicting opinions and views became commonplace.

While a handful of new studies showed that oat bran had tangible healing benefits, one study reported an 'alarming' finding – that oat bran could trigger intestinal distress.

To highlight another paradigm: the great coffee miracle and dilemma. One study concluded that coffee, the cuppa that cheers, could be a likely trigger for more than half of all pancreatic cancers. Follow-up studies showed the whole idea was flawed. What do we have now? New studies have revealed the goodness of coffee in improving our reflexes, memory and reasoning power, along with the brew's protective 'cascade' on healthy cells, following radiation therapy.

This is cheering news for coffee lovers – but, again, the jury is guarded. A body of research now suggests that the better part of valour is discretion. The best thing to do, they argue, is to sip not more than 3-4 cups of coffee every day.

Let us now examine the billion-rupee question in detail. How can science, or medicine, in the wake of conflicting evidence, get to the 'root', or truth, of scientific reality and persuade people not to throw up their arms in disgust? One plausible answer is meta-analysis.

What's more, modern science demands it. Because, the tools for making sense of reams – nay oceans – of data collected through painstaking scientific studies, are already available in the practice of meta-analysis.

Yes, all of us know that clinicians, physicians and others are up against a huge challenge – the overwhelming wealth of information, even in taut, small areas of speciality interest.

Reviews designed to summarise the outsized volumes of information are, as a result, frequently published.

When a review is done systematically, following certain criteria, and the results are pooled and analysed quantitatively, it becomes meta-analysis. A well-designed meta-analysis not only provides valuable information for researchers, clinicians, the pharmaceutical industry, and others, including policy-makers, but also a host of decisive caveats in performing and interpreting them to the best extent possible.

Yet, a major limitation continues to haunt the scientific community. Meta-analysis is not a panacea.

It is, at best, a useful 'tool'. Meta-analysis is well-established in medicine, all right – although the whole idea got its first major boost in the social and behavioural sciences.

Besides, there is a huge upside. Take, for instance, the meta-analysis on aspirin and other anti-coagulant drugs in the 1970s, which provided a 'prop' for the efficacy of the former, when taken together with the latter. It just took two years for the US Food and Drug Administration (FDA), thereafter, to approve the use of aspirin for survivors of myocardial infarction.

If only the use of meta-analysis for aspirin had been established a good 25 years before, it could have saved over 15,000 lives every year in the US alone.

To pick another typical example –the meta-analysis on the therapeutic effectiveness of streptokinase in heart attack. This is how it all happened and emerged – nearly eight previous studies did not significantly confirm the drug's beneficial effects. Conversely, a meta-analysis showed that streptokinase lowered death rates for patients treated immediately after symptoms of a heart attack occurred. This was a shot in the arm for medicine.

The streptokinase perestroika exemplified the promise the potent antioxidant, coenzyme Q10 (CoQ10), holds as a supplement in the treatment of hypertension – a 'solid ground' for meta-analysis, including the 'big leap' to exploring new theories to deciphering and analysing possibilities and variations between subject populations and also augmenting therapies in ways that would be next to impossible in just one isolated study – howsoever immaculate, or meticulous.

All said and done, meta-analysis has its share of critics, all right. Detractors call it philosophical, or prejudiced, with its 'hard' and 'soft' end-points – or, publication bias, because studies that show 'positive' results – usually in favour of a new treatment, or against a well-established protocol – are more likely to be published than those that do not. Yet, despite its pitfalls, most scientific observers reckon that meta-analysis is the best possible tool there is – and, that it is a definitive advance for better protocols to emerge in the future.

Nidamboor is a wellness physician, independent researcher and author

A version of this article appears in the print on July 29 2021, of The Himalayan Times.